Interleukin-1 beta and granulocyte-macrophage colony-stimulating factor mediate Langerhans cell maturation...

It has been reported that the in vivo maturation of Langerhans cells after hapten painting is mediated by IL-1 beta while Langerhans cell maturation after in vitro culture is mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF). To clarify the reason for this discrepancy, we examine the expression of Ia antigen and several co-stimulatory molecules on Langerhans cells that were activated by in vitro culture, by hapten painting, or by an intradermal injection of several cytokines. Both cultured Langerhans cells and those activated by hapten painting increased the expression of Ia antigen and all the co-stimulatory molecules (i.e., intercellular adhesion molecule-1 [ICAM-1], B7-1, B7-2, and CD40). In contrast, an intradermal injection of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) increased the expression of Ia antigen, ICAM-1, B7-2, and CD40, but not that of B7-1. These data indicate that IL-1 beta or TNF-alpha is not sufficient to induce B7-1 expression on Langerhans cells in vivo. Subsequently we examined the effect of anti-cytokine antibodies (Abs) on the expression of those molecules on cultured Langerhans cells. While none of the Abs to IL-1 beta, TNF-alpha, or GM-CSF changed the upregulation of Ia antigen, ICAM-1, or CD40 on cultured Langerhans cells, anti-GM-CSF Ab suppressed that of B7-1 and B7-2. Taken together, our present results suggest that IL-1 beta is required for the upregulation of Ia, ICAM-1, B7-2, and CD40, while GM-CSF is required for the upregulation of B7-1 and B7-2, although it still remains unclear why the injected GM-CSF could not augment B7-1 expression on Langerhans cells in vivo and why anti-IL-1 beta Ab did not suppress the upregulation of Ia, ICAM-1, or CD40 on cultured Langerhans cells.